Objective: To investigate the significance in the early diagnosis of Aβ_1-42, AGEs and sRAGE in serum of patients with AD. Method: 88 qualified subjects were enrolled and divided into normal group (CDR = 0) 29 cases, mild cognitive impairment (MCI) group 30 cases (CDR = 0.5), Dementia group (CDR ≥ 1) 29 cases according to clinical Dementia Rating scale (CDR). Serum level of Aβ_1-42、advanced glycation end products (AGEs) and Soluble receptor for advanced glycation end products (sRAGE) were measured and their relationships with cognitive impairment were analyzed. All data was processed by SPSS 22.0. Results: Aβ_1-42 values: Serum Aβ_1-42 levels in the MCI group and dementia group were significantly lower than those in the normal group (P<0.01), and the Aβ_1-42 levels in the dementia group were significantly lower than those in the MCI group (P<0.01). AGEs value: The serum AGEs level of MCI group (P<0.05) and dementia group was significantly lower than that of normal group (P<0.01); the serum AGEs level of MCI group was significantly higher than that of dementia group (P<0.05). Compared with the dementia group, the serum sRAGE level in the normal sRAGE group (P<0.01) and the MCI group (P<0.05) decreased significantly. In this study, the patient's serum Aβ_1-42 levels were significantly positively correlated with the (Mini Mental State Examinatin,MMSE) and the Montreal Cognitive Assessment Scale (MoCA) scores (r=0.372, P<0.01, r=0.442, P< 0.01); serum AGEs levels are positively correlated with MMSE and MoCA scores (r=0.237, P<0.05; r=0.221, P<0.05); serum sRAGE levels are negatively correlated with MoCA and MMSE scores (r=-0.260, P< 0.05; r=-0.244, P<0.05). Conclusion: The serum levels of Aβ_1-42, AGEs and sRAGE in AD patients gradually decreased with the progression of the disease. In the early diagnosis of AD the serum levels of Aβ_1-42 were specific and sensitive, the serum levels of AGEs were helpful to some extent, while the serum levels of sRAGE had less reference value.